A central activity of the ongoing human genome project is the construction of maps for all human chromosomes en route to the eventual elucidation of their complete DNA sequence. The major ongoing project in the Physical Mapping Section aims to establish a fully integrated and highly annotated physical map of the 170-megabase human chromosome 7 and to utilize the resulting information for studying important biological problems. Our general mapping paradigm involves the detection of PCR-based landmarks called sequence-tagged sites (STSs) within large (100,000 to >1,000,000 bp) fragments of DNA cloned into yeast artificial chromosomes (YACs). We have developed and implemented strategies that allowed the generation of over 2000 chromosome 7-specific STSs as well as a set of over 5000 YACs highly enriched for human chromosome 7 DNA. Cross referencing the STSs with the YACs has allowed the assembly of a modest number of YAC contigs. The evolving physical map has also been rigorously integrated with the cytogenetic and genetics maps of the chromosome. Analysis of the data indicates that upwards of 98% of the chromosome is accounted for in the existing YAC contigs. Furthermore, 91% of the chromosome is accounted for by the 50 YAC contigs that are anchored on the genetic map (in other words, 91% of the chromosome has been mapped on contigs that are ordered and mostly oriented relative to the centromere and telomeres). A major emphasis is now being placed on the localization of gene sequences on these evolving contig maps. Furthermore, the maps and associated reagents are being actively used to study regions of chromosome 7 associated with human genetic diseases, including retinitis pigmentosa (2 loci), Williams syndrome, cerebral cavernous malformations, and several other disease loci. Initial efforts are underway to establish a higher-resolution physical map of the chromosome that can be used for the initiation of large-scale DNA sequencing.